tbuckley/cabot-search huggingface dataset:
Abstract 15835: Deep Learning Based Personalized Treatment Recommender System for HFpEF Patients in the TOPCAT Americas Population
Authors: Areeb Gani, Nuha Gani, Gauri Dandi, Ian Atkinson, Zyannah Mallick, Victoria Xin, Anwar Husain, Yves Rosenberg, Ahmed A Hasan
Journal: Circulation (2022)

Introduction: The NHLBI supported TOPCAT trial (NCT00094302) investigated whether treatment with spironolactone (SPL) reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and preserved ejection fraction (HFpEF). We reused publicly available patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses with deep learning (DL) on the American TOPCAT cohort to generate treatment recommendations for HFpEF. Methods: Clinical phenogroups based on baseline characteristics of the American TOPCAT cohort (n = 1,053) were created using KPrototypes, suited for mixed data clustering. Treatment outcomes were assessed for hHF by DeepSurv, a DL generalization of Cox proportional hazards model, and Random Survival Forest (RSF), a tree-based survival analysis model. Comparison of survival probabilities from both models was used to create a recommender system used to guide treatments. Results: Cluster 1 was composed of younger patients with high cardiometabolic risk compared with Cluster 2. Diabetic patients (type 1 and type 2) comprised 93.2% of patients in cluster 1 and 10.1% of patients in Cluster 2. Among both clusters, DeepSurv and RSF trained well based on calculated C-indices, with DeepSurv often outperforming the RSF model (C-index = 0.797 vs. 0.698). Both approaches corroborated with each other and recommended the SPL treatment for the majority of patients in Cluster 1 (Figure 1). The models also recommended the SPL treatment for the majority of patients in cluster 2, although DeepSurv was less confident in this suggestion than RSF (Figure 1). Conclusions: This preliminary analysis shows the potential effectiveness of tailoring SPL as a treatment for HFpEF. The efficacy of deep learning models shows how advanced techniques can be used to promote precision medicine. Further analyses will be done to establish guided treatment efficacy in DL-generated subgroups of HFpEF patients.
Abstract 239: Evaluation Of A Shock Advisory Algorithm In An Automated External Defibrillator Using Real-world Data
Authors: Mengqi Gao, Chenguang Liu, Stacy Gehman, Dawn Jorgenson
Journal: Circulation (2022)

Objective: Studies have shown that survival rate can be increased with AED deployment, but delivering a shock to patients who may not need one can be harmful. Thus, it is important to evaluate AED shock advisory algorithms in real-world use. This study reports the retrospective performance from out-of-hospital uses of the Philips SMART Analysis algorithm in the FR3 AED. Methods: A representative sample of 1,619 de-identified patient uses from four emergency medical services agencies in the United States, between 2015 and 2017, were included in this study. In each case, the first analysis by the SMART Analysis algorithm was always extracted, and a second analysis was randomly selected among the subsequent analyses (if any), resulting in a total of 2,739 analyses. All analyses were independently annotated by three clinical experts who were blinded to AED advisories (shock advised/no-shock advised). Based on the annotations, analyses with undeterminable rhythms or without an AED advisory were excluded. The recorded AED advisories were compared against the rhythm annotations. Results: Among the 2,739 analyses, a total of 2,616 (95.5%) were included in this study. Based on the consensus among the experts, there were 12.4% (324/2,616) annotated as shockable rhythms, 84.3% (2,205/2,616) non-shockable and the remaining were intermediate rhythms (benefits of shock are uncertain). The overall sensitivity and specificity (n/N, 90% one-sided LCL) were 96.3% (312/324, 95.0%) and 99.9% (2,202/2,205, 99.8%), respectively. The algorithm performance in each rhythm category is shown in Table 1. Conclusions: This study demonstrates that the Philips SMART Analysis algorithm in FR3 AEDs has a high sensitivity to detect shockable rhythms while maintaining a near 100% specificity for non-shockable rhythms. The algorithm’s real-world performance exceeds the requirements in the American Heart Association (AHA) guidelines and shows the safety and effectiveness of the algorithm.
Abstract 15656: Genotype-Specific Natural History of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Andrea Mazzanti, Deni Kukavica, Alessandro Trancuccio, Gala Giannini, Mirella Memmi, Patrick Gambelli, Raffaella Bloise, Maira Marino, Massimo Morini, Martin F Ortiz, Carlo Napolitano, Silvia G Priori
Journal: Circulation (2022)

Background: Based on the genetic background, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) has been recently classified in “typical” (RYR2 and CASQ2) and “atypical” (TRDN, TECRL, CALM1-3, RYR2 loss-of-function [RYR2-LoF]), but genotype-specific outcome is unknown.Hypothesis. We aimed to describe genotype-specific outcomes of patients with “typical” and “atypical” CPVT before treatment. Methods: Patients were classified in: 1) “Typical” CPVT (RYR2, CASQ2); 2) “Atypical” CPVT (TRDN, TECRL, CALM1-3 and RYR2-LoF). We assessed the occurrence of a first life-threatening arrhythmic event (LAE; sudden cardiac death, aborted cardiac arrest or hemodynamically non-tolerated ventricular tachycardia) before the initiation of therapy. We used the Kaplan-Meier life-table method and the log-rank test to compare the cumulative probability of experiencing a first LAE by the age of 40 years in the absence of treatment. Results: We included 238 patients (56% females, median age 14 years [IQR: 9-28 years]): 226/238 (95%) patients with “typical” CPVT (216 RYR2, 10 CASQ2), and 12/238 (5%) patients with “atypical” CPVT (5 RYR2-LoF, 4 TRDN, 3 TECRL). Interestingly, in 47% of probands the RYR2 variant was likely de novo. No patients experienced an LAE in the first year of age, but patients with atypical CPVT had an increased probability to experience a LAE by the age of 5 years (3/5, 60%), as compared with patients with typical CPVT (2/43, 5%; OR 30.8; p=0.003). In half of patients with LAE (23/48; 48%), the occurrence of LAE was the first clinical manifestation of CPVT. Overall, the probability to experience an LAE by the age of 40 years in the absence of treatment was higher in patients with atypical CPVT (100%), as compared to patients with typical CPVT (39%; p=0.003, Figure). Conclusions: Patients with atypical variants of CPVT are at increased risk to experience an LAE before treatment, especially during early childhood.
Abstract 15842: Interplay of Genomic and Conventional Risk for Cardiometabolic Disease in Saudi Arabia
Authors: Injeong Shim, Hiroyuki Kuwahara, NingNing Chen, Mais Hashem, Lama AlAbdi, Xin Gao, Mohamed AbouElHoda, Hong-Hee Won, Pradeep Natarajan, Patrick T Ellinor, Amit V Khera, Fowzan S Alkuraya, AKL C FAHED
Journal: Circulation (2022)

Introduction: Saudi Arabia is the largest country in the Middle East and has an alarming rise in cardiometabolic disease. While conventional risk factors are highly prevalent, it is not clear if and how genomic risk might be playing a role. Methods: In 5,399 Saudi patients (age 54.8±14.8 years, 35.7% female) referred for cardiac catheterization, we collected detailed cardiometabolic phenotype data and performed whole-genome genotyping. We implemented a computational framework to develop Arab-specific polygenic scores for 9 traits (Figure A, B). We studied the association of the polygenic scores with cardiometabolic disease, and their interplay with conventional risk factors using regression models adjusted for age, sex, and genetic ancestry. Results: Within this disease cohort with high prevalence of conventional risk factors - 65.0% coronary artery disease (CAD), 55.6% type 2 diabetes (DM-2), 41.5% obesity, 48.8% hypercholesterolemia, 80.6% hypertension, and 38.3% smoking - polygenic scores were strongly associated with cardiometabolic traits (Figure C). The effect sizes of polygenic scores for CAD and DM-2 remained unchanged with adjustment for clinical risk factors. Genomic risk was also associated with the severity of CAD, as measured by the number of vessels with severe stenosis on cardiac catheterization (Figure D). CAD patients with high genomic risk - defined as top quintile of the polygenic score - (N=568) had earlier onset (54.8 vs. 57.9 years, p=0.001) and more severe disease (41.3% vs. 29.9% with three-vessel CAD, p&lt;0.001) despite similar clinical risk factors, compared to CAD patients without high genomic risk (N=1144). Conclusions: Polygenic scores were strongly associated with cardiometabolic disease even in a non-European population with high prevalence of conventional risk factors. Genomic risk for CAD appears independent of conventional risk factors and identifies patients with earlier onset and more severe disease.
Abstract 210: Norepinephrine Versus Epinephrine For Post-Cardiac Arrest Shock In The Prehospital Setting: A Retrospective Analysis
Authors: Emma R Wender, Ryan A Cocca, Catherine Counts, Michael R Sayre, Charles Maynard, Nicholas J Johnson
Journal: Circulation (2022)

Introduction: Shock after out-of-hospital cardiac arrest (OHCA) is common and often treated with vasopressors. Compared with norepinephrine (NOR), infusion of epinephrine (EPI) is associated with higher mortality and morbidity among hospitalized patients; but the optimal prehospital approach is unknown. We sought to examine whether infusion of EPI versus NOR is associated with neurologically-intact survival among OHCA patients. Methods: This retrospective cohort study included transported OHCA cases in Seattle, WA from 2014-2021 who received advanced life support. Our primary exposure was infusion of EPI or NOR. Our primary outcome was neurologically-favorable survival (Cerebral Performance Category score of 1 or 2) to hospital discharge. Key secondary outcomes were prehospital rearrest, survival to hospital admission, and hospital mortality. We conducted multivariable logistic regression adjusting for baseline patient and OHCA characteristics. Results: Of 1784 OHCA patients, 263 (15%) received NOR and 201 (11%) received EPI infusions, 18 received both, and 1298 received neither. Those who received EPI were older (median 65 [IQR 52-78] vs 62 [IQR 47-75] years), but otherwise had similar baseline characteristics, including initial arrest rhythm (Table 1). Patients who received EPI were over twice as likely to have rearrested in the prehospital setting (53% vs 24%). After adjustment, there was no difference in neurologically-favorable survival (OR 0.91, 95% CI 0.47-1.78). We found no difference in survival to hospital admission or discharge. Conclusion: Neurologically-favorable survival was similar among patients who received NOR or EPI infusions for post-OHCA shock, though patients who received EPI had prehospital rearrests more often. Future trials should examine the optimal approach to hemodynamic management for post-OHCA shock.
Abstract 15519: Site- and Cell-Selective Treatment of Atherosclerosis Using a Combination of RNA Therapeutic Approaches
Authors: Isabella Hetherington, Jeffrey VanWye, Ishani Wickramage, Ismet Hortu, Hana Totary-jain
Journal: Circulation (2022)

Atherosclerotic plaque formation in the arteries underlies acute coronary syndromes (ACS); therapies to treat atherosclerosis that are both site- and cell-selective are not available. The CANTOS clinical trial demonstrated the benefits of targeting inflammation to reduce adverse cardiac events, but the systemic immune suppression increased incidence of sepsis or death caused by infections, highlighting the need for local inflammation inhibition. To assess the local chronic inflammatory state associated with atherosclerotic plaques, coronary arteries were isolated from non-transplantable human hearts ( Fig. A) from donors ranging in age from 6-months to 72 years old. Donors aged 51-72 had various conditions including hypertension, hypercholesterolemia, and atherosclerosis. Strikingly, qPCR analysis showed an increase in interleukin 1 beta (IL-1β) mRNA levels corresponding to increasing age of the donor and presence of CVD risk factors, with almost a 20-fold increase in the 72 compared to the 6-month-old donor ( Fig. B ).To specifically target the atherosclerotic plaques and the plaque forming cells without affecting the endothelium, we used a cell-penetrating peptide (p5RHH) ( Fig. C ) that self-assembles with synthetic mRNA to form nanoparticles that exclusively target denuded regions of endothelium and atherosclerotic plaques ( Fig. D ). We will deliver small interfering RNA specific to IL-1β and a microRNA switch that consists of synthetic mRNA encoding a cell-cycle inhibitor, p27, that includes a single target site for the endothelial cell specific miR-126, which we previously showed to selectively inhibit intimal hyperplasia and infiltrating immune cells while sparing the vascular endothelium ( Fig. E ). This innovative combination of multiple RNA therapeutics into a single nanoparticle will advance the field of site- and cell-selective anti-atherosclerotic therapy.
Abstract 15924: Intelligent Machine Learning Fusion Framework Predicts Atrial Fibrillation Ablation Outcomes With Demographic, Morphological, and Imaging Features
Authors: Muhammad Fazal, Albert J Rogers, Ridhima Kapoor, Paul J Wang, Sanjiv M Narayan, Orod Razeghi, Tina Baykaner
Journal: Circulation (2022)

Background: Structural changes in the left atrium (LA) modestly predict outcomes in patients undergoing catheter ablation for atrial fibrillation (AF). Machine learning (ML) is a promising approach to improve risk prediction based on complex and variable data inputs.Hypothesis: We hypothesized that ML approaches based on a patient's specific atrial morphology from cardiac computed tomography (CT) and clinical data can predict response to AF ablation. Methods: Consecutive patients undergoing AF ablation from 2014-2017 with preprocedural CT scans and long-term clinical follow-up were included in the retrospective analysis. A fusion model incorporated demographic data with morphologic and 3D imaging classifiers based on an automatous segmentation of CT scans to predict arrhythmia recurrence after catheter ablation of AF. LA morphologic features were derived from left atrial segmentation. The LA image classifier was developed using a 3D image convolutional neural network. Multi-modal data sources were fused in a framework that determines individual importance and optimizes classification. Results: 321 patients (64.2 + 10.6 years, 69% male, 40% paroxysmal AF) were analyzed. Post 10-fold nested cross-validation, the model trained to intelligently fuse and learn appropriate weights for clinical, morphological, and imaging data (AUC 0.81±0.02) outperformed those trained solely on clinical data (AUC 0.61±0.04), morphological (AUC 0.68±0.10) or imaging data (AUC 0.75±0.02). Conclusion: In the context of clinical data, information from atrial geometry from CT imaging improved risk prediction of AF recurrence in patients undergoing catheter ablation using an ML based-fusion framework model. The fusion technique allowed improved patient-specific prediction of clinical models and may inform therapy selection with non-invasive tools
Abstract 15499: Adjunctive Papillary Muscle Approximation With Undersizing Mitral Annuloplasty Improves Mitral Valve Mobility and Biomechanics to Repair Functional Mitral Regurgitation
Authors: Gediminas Gaidulis, Muralidhar Padala
Journal: Circulation (2022)

Introduction: Undersizing mitral annuloplasty (UMA) to repair functional mitral regurgitation (FMR) has failed to achieve durable results. Though FMR recurrence rates of 60% at 2 years are often cited, even at 30 days, nearly 30% of the patients had moderate or greater FMR in the CTSN trial. We previously demonstrated experimentally that adjunctive papillary muscle approximation (PMA) can improve valve function, with or without UMA. In this modeling study, we used patient specific mitral valve geometries to investigate the effects of UMA and UMA+PMA on mitral valve biomechanics. Methods: 3D ultrasound was obtained in 3 pigs with chronic heart failure and moderate or severe FMR. Each 3D echo was segmented, and computational valve models were developed. UMA was mimicked with ring sizes of 36, 32, and 28 mm ( Fig A ). PMA was then added to each ring size, and the outcomes were reassessed ( Fig B ). In each simulation, leaflet stresses and chordal forces, coaptation area, and tenting parameters were computed. Results: Compared to pre-repair, UMA increased coaptation area by 178.3% with 36 mm, 279.1% with 32 mm, and 356.7% with 28 mm ring ( Fig C ). With 36 mm ring, leaflet stresses increased by 4.3%, while smaller rings reduced stresses by 24.3% (32 mm) and 33.8% (28 mm) ( Fig D ). Chordal forces after UMA decreased by 37.6%, 50.6%, and 55.2% ( Fig E ). Leaflet mobility was improved, as tenting area decreased by 46.1%, 57.9%, and 67.5% ( Fig F ). Adding PMA, achieved better valve closure and coaptation without the need for excessive annular downsizing: tenting area decreased by 76.5%, 85.2%, and 92%, and coaptation area increased by 190.6%, 309.8%, and 386.4%. In addition, leaflet stresses were reduced by 17.4%, 38.5%, and 44.9%, and chordal forces by 48.1%, 63.7%, and 72.9%. Conclusions: Adjunctive addition of PMA repaired FMR and restored physiological mitral valve mobility even at 36 mm annular size, reducing the need for excessive annular undersizing and potentially resulting in a durable repair.
Abstract 15564: Transcriptional Profiling Unveils New Molecular Subgroups of Adaptive and Maladaptive Right Ventricular Remodeling in Pulmonary Hypertension
Authors: Fatemeh Khassafi, Prakash Chelladurai, Sreenath R Nayakanti, Sandra Martineau, Khodr Tello, Natascha Sommer, Junichi Omura, Sandra Breuils Bonnet, Carsten Kuenne, Stefan Guenther, francois potus, Olivier Boucherat, Steeve Provencher, Rajkumar Savai, Werner Seeger, Mario Looso, Sebastien Bonnet, Soni Savai Pullamsetti
Journal: Circulation (2022)

The right ventricle (RV) function plays a crucial role in the prognosis and functional outcome of PAH (Pulmonary Arterial Hypertension) patients. However, RV remodeling and its underlying mechanisms in PAH, and the molecular phenotype of RV in different disease conditions are poorly understood. Therefore, we designed this study to deeply investigate molecular changes underlying right ventricular remodeling and dysfunction in PAH. To this aim, we generated RNA-seq data from 40 patients' RV tissues, clinically classified in adaptive versus maladaptive RV hypertrophy. Using an unsupervised clustering-based analysis, we identified “early” and “late” subgroups in both diseased RV states, associated with patients’ hemodynamic profiles. We then demonstrated that the compensated RV is characterized by an upregulation of cell cycle-associated genes and mitochondrial respiration, whereas excessive levels of extracellular matrix components were central in the decompensation phase. However, dysregulation of fatty acid β-oxidation characterized the early decompensation phase. Furthermore, a comparative analysis from 30 RV samples of monocrotaline (MCT)-induced rat model largely confirmed the stage-specific molecular phenotypes, along with subgroups identification. Finally, we assessed the circulating levels of several dysregulated proteins in two independent cohorts of PAH patients and introduced a panel of five ECM-related proteins that had a significant alteration in patients with compensated vs. decompensated RV in both cohorts. Among those, NID1, C1QTNF1, and CRTAC1 demonstrated higher importance in predicting the development of maladaptive RV hypertrophy in both cohorts, while the correlation of their expression with cardiac functions confirmed their potential biomarker capacity in the prognosis of PAH-associated RV hypertrophy and failure. In conclusion, this comprehensive transcriptome study revealed new subgroups of human RV hypertrophy beyond the clinical measurements, while combination with proteome analysis proposed a panel of potential PAH biomarkers related to patients' RV function. Furthermore, our comparative analysis of two species supports the relevance of current animal models to explore new targets.
Abstract 15665: Pod-Based Electronic Cigarette Use Alters Measures of Heart Rate Variability
Authors: Chelsea Akubo, Sana A Majid, Robert M Weisbrod, Sanjay Srivastava, Jessica L Fetterman, Daniel J Conklin, Rose M Robertson, Aruni Bhatnagar, Rachel J Keith, Naomi M Hamburg
Journal: Circulation (2022)

Background: Previous studies demonstrate changes in autonomic function with combustible and earlier generation electronic cigarette (ecig) use. We sought to explore the effects of nicotine salt containing pod-based ecigs on autonomic regulation in young adult regular users by analyzing indices of heart rate variability (HRV). Methods: We enrolled healthy adults (18-45 yo) who were self-reported tobacco nonusers, pod-based ecig users, or combustible cigarette users. Participants were asked to refrain from tobacco product use at least 6 h before the study visit. Indices of HRV: standard deviation of the NN intervals (SDNN) and the root mean square differences of successive NN intervals (RMSSD, measure of parasympathetic function) were measured by Sphygmacor before and 10 minutes after structured use of participants’ own product. Measurements of urinary levels of cotinine, a nicotine metabolite, and 3HPMA, an acrolein metabolite, were made 1 h after product use. Results: In 133 subjects (age 26±5, 49% women), baseline HRV measures were comparable among tobacco non-users (N=39), pod-based ecig users (N=64), and combustible cigarette users (N=30). Analyses adjusted for age and sex demonstrated that acute pod-based ecig use reduced SDNN compared with non-use (-5.9±2.6ms vs 6.5±3.2ms, P=0.004) and similar to the effect of combustible cigarette use (-10.2±3.8ms, P=0.37). Moreover, acute pod-based ecig use reduced RMSSD compared with non-use (-5.6±3.3ms vs 5.4±4.1ms, P=0.04) and similar to the effect of combustible cigarette use (-10.9±4.9ms, P=0.38). Urinary cotinine, reflective of nicotine exposure, was associated with decreases in SDNN and RMSSD (r=-0.33, P=0.001; r=-0.29,P=0.003, respectively) whereas 3HPMA associated with SDNN and showed a trend toward association with RMSSD (r=-0.27, P=0.006; r=-0.18, P=0.06, respectively). Conclusion: Our data demonstrate an association between acute use of pod-based ecigs and altered cardiac autonomic function in association with the level of nicotine and acrolein exposure.